Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

NCT00049023 | Completed Phase 1 DMC

• 3 other identifiers: 200008086UIHC-200008086NCI-V02-1710
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Radiolabeled octreotide can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells. PURPOSE: This phase I trial is to study the safety and effectiveness of radiolabeled octreotide in treating children who have advanced or refractory solid tumors.

Conditions

Brain and Central Nervous System Tumors; Gastrointestinal Carcinoid Tumor; Islet Cell Tumor; Neuroblastoma; Pheochromocytoma; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

childhood grade III meningioma; disseminated neuroblastoma; localized unresectable neuroblastoma; metastatic pheochromocytoma; metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent childhood brain tumor; recurrent childhood medulloblastoma; recurrent neuroblastoma; recurrent pheochromocytoma; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; regional neuroblastoma; regional pheochromocytoma; unspecified childhood solid tumor, protocol specific; recurrent childhood ependymoma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; recurrent islet cell carcinoma; gastrinoma; insulinoma; metastatic gastrointestinal carcinoid tumor; recurrent gastrointestinal carcinoid tumor; regional gastrointestinal carcinoid tumor

Outcome Measures

Primary Outcomes (2)

• Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide

  Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors based upon the 6 week/cycle dose-limiting-toxicity profile.

  6 weeks per cycle

• Evaluate the short term and long term safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events)

  2\. Evaluate the short-term (6 weeks/cycle) and long term (4-6 months) safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events) serious adverse event profile of three-cycles of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors.

  short term (6 weeks/cycle); long term (4-6 mos./cycle)

Study Arms (1)

90Y-DOTA-tyr3-OCTREOTIDE

EXPERIMENTAL

Dose escalation will proceed so that the single-cycle and three-cycle maximum tolerated doses of 90Y-DOTA-tyr3-Octreotide can be determined. The initial dose of 90Y-DOTA-tyr3-Octreotide to be administered is 30 mCi/m2 in each of three cycles. Dose escalation will proceed in 10 mCi/m2 intervals and will be permitted for the next cohort of subjects pending completion of Cycle 3 by 2 members of the previous cohort with no DLTs. A DLT is defined as a Grade 3 renal toxicity, Grade 4 bone marrow toxicity, or any other Grade 3 toxicity whether or not related to study drug and regardless of duration. Lymphopenia will not be used to define a DLT.

Radiation: 90Y-DOTA-tyr3-OCTREOTIDE

Interventions

90Y-DOTA-tyr3-OCTREOTIDE RADIATION

90Y-DOTA-tyr3-OCTREOTIDE

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed malignant neoplasm * Not amenable to standard therapy or has failed existing first- and second-line therapies * Tumor positive for somatostatin receptors by OctreoScan within the past 4 weeks * At least 1 measurable lesion * Lesions that have been previously irradiated must demonstrate progression since radiation * At least 1 measurable somatostatin receptor-positive lesion that has not been irradiated within the past 4 weeks AND has not had full craniospinal radiation within the past 3 months * Bone marrow with at least 40% cellularity OR at least 20% cellularity with one million CD34+ stem cells/kg stored * No diffuse bone marrow involvement by OctreoScan scintigraphy PATIENT CHARACTERISTICS: Age * 2 to 25 Performance status * COG 0-2 OR * Karnofsky 60-100% OR * Lansky 60-100% Life expectancy * 2-12 months Hematopoietic * See Disease Characteristics * Absolute neutrophil count at least 1,000/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic * Bilirubin less than 1.5 times normal * AST and ALT less than 2.5 times upper limit of normal Renal * Creatinine no greater than 1 mg/dL (children less than 5 years of age) * Creatinine less than 1.2 mg/dL (children 5 to 10 years of age) * Creatinine less than 1.7 mg/dL (children over 10 years of age) AND * Glomerular filtration rate at least 80 mL/min/m\^2 Cardiovascular * Shortening fraction at least 28% by echocardiogram * Ejection fraction at least 50% by bi-plane method of echocardiogram * No prior congestive heart failure unless ejection fraction at least 40% * No unstable angina pectoris * No cardiac arrhythmia * No symptomatic congestive heart failure Other * No other concurrent malignancy * No other significant uncontrolled medical, psychiatric, or surgical condition that would preclude study compliance * No antibodies to yttrium Y 90-DOTA-tyr3-octreotide or octreotide * No prior allergic reactions to compounds of similar chemical or biologic composition to yttrium Y 90-DOTA-tyr3-octreotide * No ongoing or active infection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) Endocrine therapy * More than 28 days since prior long-acting somatostatin analogues * No concurrent somatostatin analogues 12 hours before or 12 hours after study drug administration * Concurrent hormonal therapy (other than somatostatin analogue) allowed provided patient received hormonal therapy for at least 2 months and has stable disease or progressive disease Radiotherapy * See Disease Characteristics * At least 4 weeks since prior radiotherapy * No prior radiotherapy to 25% or more of bone marrow * No prior external beam radiotherapy to both kidneys (scatter doses of less than 500 cGy to a single kidney or radiation to less than 50% of a single kidney is allowed) Surgery * At least 4 weeks since prior surgery Other * Recovered from prior therapy * At least 4 weeks since prior investigational drugs * No other concurrent approved or investigational anti-neoplastic therapies except for bisphosphonates * No concurrent combination antiretroviral therapy for HIV-positive patients

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• O'Dorisio, M S: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

Related Publications (1)

• Menda Y, O'Dorisio MS, Kao S, Khanna G, Michael S, Connolly M, Babich J, O'Dorisio T, Bushnell D, Madsen M. Phase I trial of 90Y-DOTATOC therapy in children and young adults with refractory solid tumors that express somatostatin receptors. J Nucl Med. 2010 Oct;51(10):1524-31. doi: 10.2967/jnumed.110.075226. Epub 2010 Sep 16.

  PMID: 20847174 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Adenoma, Islet Cell; Neuroblastoma; Pheochromocytoma; Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Medulloblastoma; Familial ependymoma; Carcinoma, Islet Cell; Gastrinoma; Insulinoma

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pancreatic Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Paraganglioma; Neuroendocrine Tumors; Neoplasms, Connective and Soft Tissue; Glioma; Adenocarcinoma; Carcinoma

Study Officials

• M. Sue O'Dorisio, MD, PhD

  Holden Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 12, 2002
• First Posted: January 27, 2003
• Study Start: January 1, 2002
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: June 21, 2016

Record last verified: 2016-06

Locations

US (1)